Clinical significance of tumor-infiltrating lymphocytes in neoplastic progression and lymph node metastasis of human breast cancer.

To investigate the clinical significance of tumor-infiltrating lymphocytes (TILs) within the tumor milieu, we quantitatively measured and compared the subpopulations of TILs in 24 patients with stage I-III breast carcinoma. Peripheral blood mononuclear cells (PBMCs), normal breast parenchyma-infiltrating lymphocytes (NILs), and TILs were isolated from tissue specimens and quantified by flow cytometry. The results showed that increased proportion of CD8(+) T cells, with decreased proportion of CD4(+) T cells, was significant in gated CD3(+) TILs as compared to autologous NILs or PBMCs (P<0.001). The tumor-infiltrating CD8(+) T cells significantly increased with stage progression, reflected in a more strongly decreased CD4/CD8 percentage (P=0.003). The CD4/CD8 percentage of TILs was strongly correlated with lymphovascular permeation and subsequent lymph node metastasis (P<0.001). Increased percentages of tumor-infiltrating CD8(+) T cells with decreased CD4/CD8 percentages are of prognostic importance for cancer progression in human breast cancer.